Oxymorphone and its hydrochloride salt have long been used as analgesics.
Oxymorphone base is conventionally prepared by O-demethylation of oxycodone. Oxymorphone base can also be prepared by oxidation of oripavine to 14-hydroxymorphinone, and reducing the 14-hydroxymorphinone to oxymorphone base. A route for the preparation of oxymorphone via oxidation of oripavine to 14-hydroxymorphinone is illustrated in Scheme 1:

Once the oxymorphone base has been prepared, it is usually reacted with an acid to produce an oxymorphone salt, typically oxymorphone hydrochloride (which is the API form in which oxymorphone is generally used therapeutically), as shown below in Scheme 2:

The oxidation step in the synthetic route illustrated in Scheme 1 can yield by-products which may be converted into other by-products during further conversion of the oxidation product (e.g., during the reaction shown in Scheme 2) or may be carried over into the final oxymorphone salt or other opioid made from the oxymorphone base, final pharmaceutical composition or final dosage form. These by-products may be undesired in the final pharmaceutical composition or final dosage form. Separation of these by-products from the final product may often be difficult, time-consuming and not volume efficient (e.g., if a separation by HPLC is required).
For example, during oxidation of oripavine to 14-hydroxymorphinone, certain by-products can be formed, in particular 8-hydroxyoxymorphone:

The 8-hydroxyoxymorphone can be converted to 14-hydroxymorphinone when HCl is added, as illustrated in Scheme 4:

Thus, the 14-hydroxymorphinone intermediate shown in Scheme 1 is not only the immediate precursor to oxymorphone, it is also often found in the final oxymorphone salt used in pharmaceutical compositions, which is usually oxymorphone hydrochloride. 14-hydroxymorphinone belongs to a class of compounds known as α,β-unsaturated ketones (ABUKs). These compounds contain a substructural component (the α,β-unsaturated ketone component) which produces a structure-activity relationship alert for genotoxicity. Their presence may be undesired in a pharmaceutical composition. Some regulatory authorities do not approve a pharmaceutical composition or dosage form for use and sale to the public if the amount of ABUKs in the pharmaceutical composition or dosage form exceeds the amount set by these authorities.
In PCT/IB2013/001541 reactions are described which allow reduction of the amount of undesired by-products caused by the oxidation step. In particular, PCT/IB2013/001541 describes the performance of the oxidation reaction in the presence of an acid HnXn−, e.g. H2SO4, such that a 14-hydroxymorphinone salt with Xn−, e.g. SO42−, as counterion is formed:

However, even under these reaction conditions, some 8-hydroxyoxymorphone might be carried over into oxymorphone in a subsequent reduction reaction.
Even in spite of the improvements achieved by recent developments like the processes described in PCT/IB2013/001541, there is still a continuing need for processes for preparing oxymorphone which exhibit a reduced amount of by-products in the final product. In particular, a process for preparing oxymorphone base with a reduced amount of 8-hydroxyoxymorphone, preferably with no (detectable) 8-hydroxyoxymorphone would be advantageous.